Entry of the toxic proteins abrin, modeccin, ricin, and diphtheria toxin into cells. I. Requirement for calcium.
In the absence of Ca2+ cells were not sensitive to the toxic proteins abrin and modeccin and the sensitivity to ricin and diphtheria toxin was reduced. Calcium deprivation had little effect on the binding and endocytosis of abrin, modeccin, and ricin. The binding of diphtheria toxin to cells was, however, reduced, Verapamil and Co2+ inhibited 45Ca2+ uptake and protected cells against abrin and modeccin at low concentrations of Ca2+. At higher Ca2+ concentrations the protection was overcome. La3+ inhibited strongly 45Ca2+ uptake and protected well against all four toxins, even at high Ca2+ concentrations. Fe3+ also afforded protection although it did not inhibit Ca2+ uptake. The Ca2+ ionophore, A23187, which strongly increases the uptake of 45Ca2+, protected cells well against abrin and modeccin, slightly against diphtheria toxin, but not against ricin. Both Ca2+ deprivation and treatment with A23187 protected well against the hybrid toxin abrin A-chain/ricin B-chain. Such treatment afforded little protection against the hybrid ricin A-chain/abrin B-chain. Apparently the protection against abrin is associated with its A-chain. The calmodulin inhibitor, trifluoperazine, protected strongly against modeccin and diphtheria toxin. The data indicate that Ca2+ is involved in the entry mechanism for abrin, modeccin, and ricin, possibly as a Ca2+ flux together with the toxins.
D000036:Abrin / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004167:Diphtheria Toxin / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007668:Kidney; D007811:Lanthanum / Q000494:pharmacology; D037102:Lectins / Q000378:metabolism*; D037121:Plant Lectins; D010940:Plant Proteins / Q000378:metabolism*; D011955:Receptors, Drug / Q000378:metabolism; D054790:Ribosome Inactivating Proteins, Type 2; D012276:Ricin / Q000378:metabolism*; D014118:Toxins, Biological / Q000378:metabolism* / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology
D004167:Diphtheria Toxin; D037102:Lectins; D037121:Plant Lectins; D010940:Plant Proteins; D011955:Receptors, Drug; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; D000036:Abrin; D014268:Trifluoperazine; D000001:Calcimycin; C016004:modeccin; D007811:Lanthanum; D012276:Ricin; D002118:Calcium